Several series of experiments are planned continuing work on the biochemistry and physiology of two neural peptides; a) substance P, first purified to homogeneity in this laboratory and b) neurotensin, another vasoactive peptide discovered and isolated in this laboratory. Both these peptides have been sequenced, synthetic material prepared that is indistinguishable from native material by multiple chemical and biological criteria, and radioimmunoassays developed. Using these RIA's, studies are planned to study the distribution of Substance P and neurotensin in brain, peripheral nerve and body fluids, e.g., blood, synovial fluid and cerebro spinal fluid, etc., and to measure any changes in the concentrations of these peptides in response to various experimental manipulations in animals as well as disease states in man in order to gain an understanding of the physiological roles of these two peptides.